Nevus Cell Aggregates in Lymph Nodes

Patterson, James W.

doi:10.1309/jxe9eyqxd691lv2y

Cited by 42 publications

(17 citation statements)

References 23 publications

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“…In a number of human melanoma patients, a population of melanocytes is detected in sentinel lymph nodes (25). Interestingly, in lymph nodes of tumor-bearing Tyr::N-Ras Q61K transgenic mice this population was also seen (Fig.…”

Section: Resultsmentioning

confidence: 82%

Metastasizing Melanoma Formation Caused by Expression of Activated N-RasQ61K on an INK4a-Deficient Background

Ackermann¹,

Frutschi²,

Kaloulis³

et al. 2005

Cancer Research

269

303

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Section: Resultsmentioning

confidence: 82%

Metastasizing Melanoma Formation Caused by Expression of Activated N-RasQ61K on an INK4a-Deficient Background

Ackermann¹,

Frutschi²,

Kaloulis³

et al. 2005

Cancer Research

269

303

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“…Two theories have been proposed to explain the origin of nodal melanocytic nevi. 29 One theory invokes the hypothesis that nodal melanocytic nevi arise from aberrant or arrested migration of neural crest cells during embryogenesis, whereas the opposing theory, or the so-called 'benign metastasis theory' attributes nodal nevi to the mechanical transport of nevus Utility of nestin and SOX2 in nodal melanocytic lesions cells from cutaneous melanocytic nevi to lymph nodes via lymphatic drainage. Even though most investigators consider these nevocellular aggregates benign because of their bland cytology and lack of malignant behavior, the presence of these melanocytes, especially in patients with a history of melanoma, can make the evaluation of sentinel lymph node biopsies challenging for practicing pathologists.…”

Section: Discussionmentioning

confidence: 99%

“…Even though most investigators consider these nevocellular aggregates benign because of their bland cytology and lack of malignant behavior, the presence of these melanocytes, especially in patients with a history of melanoma, can make the evaluation of sentinel lymph node biopsies challenging for practicing pathologists. 29 Unfortunately, immunohistochemical markers such as melan-A/ MART1, S100 protein and SOX10 demonstrated limited utility in differentiating metastatic melanomas from melanocytic nevi in lymph nodes. 13,14,16 In the present study, we showed that the neural stem/progenitor cell markers nestin and SOX2 exhibited high specificity in differentiating metastatic melanomas from nodal melanocytic nevi.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of neural stem and progenitor cell markers nestin and SOX2 in distinguishing nodal melanocytic nevi from metastatic melanomas

Chen

et al. 2013

Modern Pathology

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Sentinel lymph node evaluation is a critical component of melanoma staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. One of the well-known diagnostic pitfalls in melanoma sentinel lymph node evaluation is the presence of nodal melanocytic nevi, which has been demonstrated in up to 26% of lymphadenectomy specimens and specifically in melanoma patients. Melanocytic markers enhance the sensitivity of melanoma detection in sentinel lymph nodes. However, established markers such as anti-melan-A/MART1, S100 protein and SOX10 antibodies cannot discriminate melanoma metastasis from nodal nevi. Recent studies have demonstrated strong expression of neural stem/progenitor cell markers nestin and SOX2 in melanoma. In this study, we tested the diagnostic utility of nestin and SOX2 in differentiating metastatic melanomas from nodal nevi. Twenty-three lymph nodes with metastatic melanomas and 17 with nodal nevi were examined. Of the 23 metastatic melanomas, 18 showed diffuse and strong (3 þ ) nestin, 4 showed rare cells with strong (3 þ ) nestin, and one showed diffuse but faint (1 þ ) nestin staining. Nuclear SOX2 was positive in 13 metastatic melanomas. In contrast, 15 nodal nevi showed no nestin, and 2 showed rare cells with very faint (o1 þ ) nestin staining. SOX2 was negative in 13 nodal nevi. Overall, nestin was strongly expressed in metastatic melanomas (n ¼ 22/23; 96%), but not in nodal melanocytic nevi (n ¼ 15/17; 88%; Po0.0001). SOX2 was also expressed in metastatic melanomas (n ¼ 13/23; 57%) but not in the majority of nodal melanocytic nevi (n ¼ 13/16; 81%; P ¼ 0.02). In one lymph node harboring metastatic melan-A-negative desmoplastic melanoma, nestin and SOX2 strongly highlighted the infiltrating tumor cells, suggesting the potential clinical value of these two markers in desmoplastic melanoma lymph node biopsies. This study provides evidence that nestin and SOX2 can effectively differentiate nodal melanocytic nevi from metastatic melanomas and serve as powerful diagnostic adjuncts in melanoma staging. Modern Pathology (2013) 26, 44-53; doi:10.1038/modpathol.2012; published online 17 August 2012Keywords: metastatic melanomas; nestin; nodal melanocytic nevi; SOX2 Malignant melanoma is a malignant tumor of melanocytes that accounts for less than 10% of all skin cancer diagnoses but the majority of skin cancerrelated deaths. 1 For patients diagnosed with malignant melanoma, sentinel lymph node biopsy is an essential component of tumor staging, and lymph node status provides one of the most powerful predictors of melanoma recurrence and survival. [2][3][4] When melanoma metastasizes, a regional lymph node is the most common site, and tumor burden can range from rare tumor cells to complete effacement of lymph nodes. The presence of either micro-or macrometastasis in a single lymph node changes melanoma staging from stage I to stage III. 5 In addition, a single positive lymph node signifies a decrease in 10-year survival from 95% (stage IA) to 68% (stage II...

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“…One possibility is melanocytes. Although generally considered nonmotile, there are a small number of reports documenting their presence in low numbers in the LN of melanoma-bearing mice (56) and patients (57). However, melanocytes would be expected to stain brightly for tyrosinase based on their appearance in epidermal sheets and perhaps to appear more frequently in LN draining the tissue in which they are abundant.…”

Section: Discussionmentioning

confidence: 99%

Deletional Self-Tolerance to a Melanocyte/Melanoma Antigen Derived from Tyrosinase Is Mediated by a Radio-Resistant Cell in Peripheral and Mesenteric Lymph Nodes

Nichols

Chen

Colella

et al. 2007

The Journal of Immunology

137

195

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Self-tolerance to melanocyte differentiation Ags limits the ability to generate therapeutic antimelanoma responses. However, the mechanisms responsible for CD8 T cell tolerance to these Ags are unknown. We have used a newly generated TCR-transgenic mouse to establish the basis of tolerance to one such Ag from tyrosinase. Despite expression of tyrosinase transcripts in the thymus, central deletion does not shape the tyrosinase-specific CD8 T cell repertoire. We demonstrate that this endogenously expressed melanocyte Ag is constitutively presented in both peripheral and mesenteric lymph nodes, leading to abortive activation and deletion of tyrosinase-specific CD8 T cells. Importantly, this Ag is not presented by either radio-sensitive dendritic cells, or by radio-resistant Langerhans cells. Thus, for this endogenous Ag, cross-tolerization does not appear to be an operative mechanism. Instead, we find radioresistant tyrosinase mRNA expression in lymphoid compartments where CD8 T cell deletion occurs. This suggests that direct presentation of tyrosinase by radio-resistant lymph node resident cells is entirely responsible for tolerance to this endogenous melanocyte differentiation Ag.

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Nevus Cell Aggregates in Lymph Nodes

Cited by 42 publications

References 23 publications

Metastasizing Melanoma Formation Caused by Expression of Activated N-RasQ61K on an INK4a-Deficient Background

Metastasizing Melanoma Formation Caused by Expression of Activated N-RasQ61K on an INK4a-Deficient Background

Diagnostic utility of neural stem and progenitor cell markers nestin and SOX2 in distinguishing nodal melanocytic nevi from metastatic melanomas

Deletional Self-Tolerance to a Melanocyte/Melanoma Antigen Derived from Tyrosinase Is Mediated by a Radio-Resistant Cell in Peripheral and Mesenteric Lymph Nodes

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